1. Field of the Invention
The present invention relates generally to an apparatus and method for accelerating and signalling the event of coagulation of blood and components thereof.
This invention relates more particularly to an apparatus and method for injecting a neutralizing additive into a sample of anticoagulated blood and components thereof and, after neutralization, for accelerating and signalling the event of coagulation.
2. Description of the Prior Art
Lengthy surgical procedures, especially those requiring temporary cardiopulmonary bypasses and total body perfusion, involve blood coming into contact with many foreign surfaces, thereby necessitating pharmacological manipulation of the coagulation mechanism to prevent coagulation of the blood and its resultant catastrophic effects. It is known in the art of perfusion, that blood coagulation is a hemostatic process wherein certain factors normally passive in the bloodstream are stimulated into an active form which trigger a chemical chain of events resulting in a blood clot. A blood clot comprises a mass of fibrin threads surrounding entrapped cells. The process of coagulation is not completely understood, but it is well known in the art that coagulation occurs when blood is removed from the body and passed for example, through an extracorporal circuit.
In order to prevent coagulation during an extracorporeal bypass, various drugs may be injected into the blood. For example, sodium heparin is usually injected into patients requiring open heart surgery in order to neutralize the clotting factors. Open-heart surgery exposes blood to numerous procoagulant stimuli and requires significantly more heparin than other surgical procedures to achieve anticoagulation. Since, heparin is metabolized rapidly it has a half-life of one to two hours, and injections of heparin must be continuously made during surgery. Too little heparin will cause the diastrous effect of coagulation while too much heparin will cause an equally diastrous effect of postoperative internal bleeding or hemorrhaging.
The use of heparin and its half-life characteristics are well known in the art as found, for example, in Wright, et al, "Heparin Levels During and After Hypothermic Perfusion", 5 T. Card. Surg. 244-250 (1964).
A properly heparinized patient, therefore, has a concentration of heparin in his blood that is sufficient to prevent coagulation of blood but not great enough to cause internal bleeding. A surgeon, after acquiring experience, develops an insight for the amounts of heparin to use and when to inject additional heparin based on such parameters as height, weight, sex and blood volume of the patient. Obviously, such an approach involves a high degree of risk-taking by the patient.
After surgery is completed it becomes necessary to neutralize the heparin to prevent postoperative internal bleeding by the injection of an appropriate additive such as protamine sulfate. If administered alone, protamine is an anticoagulant. However, when given in the presence of heparin, a stable and physiologically inert salt is formed, thus neutralizing the anticoagulant activity of both drugs. Accurate determination of the amount of protamine for neutralization is required since too little or too much protamine results in anticoagulated blood and possible postoperative bleeding. The use of protamine as a postoperative neutalizer is well known in the art; see, for example, Reed & Clark, Cardiopulmonary Perfusion (1975), Library of Congress Catalog Card Number 75-7168.
After the patient is neutralized a "heparin rebound" condition may arise in which the patient's blood becomes heparinized due to a reappearance of heparin. Although heparin rebound is not fully understood, it is well known in the art, see Ellison, et al, "Heparin Rebound", 67 J. Thoracic Card. Surg. 723-729 (1974).
Heparin is commercially provided in varying concentrations depending on its potency from a variety of sources such as beef lung, beef liver, beef mucosa, and pork mucosa. Protamine is also commercially available in a variety of concentrations also emanating from a variety of sources such as the sperm of salmon and certain other fish.
The classical method of determining blood coagulation time is to determine the Lee-White clotting time. A sample of blood is inserted into a centrifuge in order to separate the serum from the blood. The serum is then inserted into a testing machine which determines the coagulation time by detecting a change in the opaqueness of the serum. The Lee-White process is a long process generally taking thirty minutes or longer and which involves excessive manual handling on foreign surfaces of the blood and the use of a centrifuge and a separate testing machine. The Lee-White method is not practical for determining clotting time parameters of anticoagulated blood.
A conventional approach for determining the amount of protamine at the conclusion of a heart-lung extracorporeal bypass is the protamine titration method as disclosed, for example, in Hurt, et al, "The Neutralization of Heparin by Protamine in Extracorporeal Circulation", 32 J. Thoracic Card. Surg. 612-619 (1956). The protamine titration method is a developed laboratory skill and involves using test tubes, known titration techniques, and visually determining the event of coagulation. The titration normally takes 15-20 minutes and is a function of the lab technician's skill.
Another conventional prior art approach uses a test tube sample of the heparinized blood in which is manually injected via a hypodermic needle a known amount of protamine. A gas is injected into the test tube mixture to accelerate coagulation, the gas acts as a foreign body which stimulates the clotting factors. When the blood coagulates a back pressure is delivered into the gas delivery system which is sensed by a pressure detector. The above approach is disclosed in Altshuler, et al, "Hemotensiometry", 18 Annals of Thoracic Surg. 516-530 (1974).
The above prior art approaches are generally primarily dependent on operator skill, and are, therefore, highly nonreproducible. In addition, the prior art approaches are slow in measuring the event of coagulation. At the conclusion of surgery involving an extracorporeal bypass, hemorrhage-related morbidity and mortality poses a constant threat to the heparinized patient. Although protamine and other additives effectively neutralize heparin, an overdose of protamine may cause internal bleeding, shock or thrombocytopenia. A patient who is rapidly neutralized after disconnecting the bypass and during the rebound stage will be in a minimum risk condition. If post operative hemmorrhaging then occurs, the cause is abnormal and generally mechanical thereby requiring further re-exploration.